STRUCTURAL REQUIREMENTS FOR ALPHA-MATING FACTOR ACTIVITY

The sexual hormone of S. cerevisiae, alpha-mating factor (alpha-MF, WH WLQLKPGQPMY) has structural homology with mammalian luteinizing hormon e releasing hormone (LHRH, pEHWSYGLRPG-NH2) and has been shown to exhi bit LHRH activity [Loumaye et al. (1982) Science 218, 1323-1325], We h ave tested whether LHRH has alpha-MF activity in yeast and found that it does not. We therefore synthesized a series of hybrid peptides of a lpha-MF and LHRH to study the structural features which determine alph a-MF and LHRH activities, A hybrid peptide consisting of the LHRH sequ ence with the C-terminal tetrapeptide (QPMY) of alpha-MF did not exhib it alpha-MF activity, Thus, the lack of alpha-MF activity of LHRH is n ot due solely to the absence of the C-terminal residues, Substitution of Lys(7) in alpha-MF with Arg, as is found in LHRH, did not affect th e alpha-MF activity, nor did an additional substitution of Trp(1) with pGlu, However, the C-terminal four amino acids of alpha-MF mere neces sary for alpha-MF activity, Our results indicate that insertion of a S er residue in position 4 as found in LHRH abolishes alpha-MF activity, These results suggest that, in addition to an intact C-terminus, corr ect spacing of the N-terminal His(2) and the C-terminus is required fo r alpha-MF activity, The hybrid peptides all exhibited less LHRH activ ity than either LHRH or alpha-MF. These structure-function studies ind icate that the structural homology between these two reproductive horm ones may not reflect an evolutionary relationship between them.